@article{ sibille_lack_2007,
  title = {Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity},
  volume = {12},
  issn = {1359-4184},
  doi = {10.1038/sj.mp.4001990},
  abstract = {Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-{HT}) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-{HT} system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-{HT}(1B) receptor (5-{HT}(1B)R), a candidate gene for 5-{HT}-mediated age-related functions. We show that the lack of 5-{HT}(1B)R (Htr1b({KO}) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b({KO}) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b({KO}) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b({KO}) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems ({IGF}-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-{HT} function, thus identifying 5-{HT} as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-{HT}.},
  language = {eng},
  number = {11},
  journal = {Molecular Psychiatry},
  author = {Sibille, E. and Su, J. and Leman, S. and Le Guisquet, A. M. and Ibarguen-Vargas, Y. and Joeyen-Waldorf, J. and Glorioso, C. and Tseng, G. C. and Pezzone, M. and Hen, R. and Belzung, C.},
  month = {November},
  year = {2007},
  pmid = {17420766},
  pmcid = {PMC2515886},
  keywords = {Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Dopamine Plasma Membrane Transport Proteins, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Hand Strength, In Situ Hybridization, Maze Learning, Mice, Mice, Knockout, Microarray Analysis, Motor Activity, Reaction Time, Receptor, Serotonin, 5-{HT}1B, Survival Analysis},
  pages = {1042--1056, 975}
}

{"_id":"3okQSEDpJK6wKZHiF","authorIDs":[],"author_short":["Sibille, E.","Su, J.","Leman, S.","Guisquet, A.<nbsp>M.<nbsp>L.","Ibarguen-Vargas, Y.","Joeyen-Waldorf, J.","Glorioso, C.","Tseng, G.<nbsp>C.","Pezzone, M.","Hen, R.","Belzung, C."],"bibbaseid":"sibille-su-leman-guisquet-ibarguenvargas-joeyenwaldorf-glorioso-tseng-pezzone-hen-belzung-lackofserotonin1breceptorexpressionleadstoagerelatedmotordysfunctionearlyonsetofbrainmolecularagingandreducedlongevity-2007","bibdata":{"abstract":"Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-HT(1B) receptor (5-HT(1B)R), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT(1B)R (Htr1b(KO) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b(KO) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b(KO) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b(KO) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT.","author":["Sibille, E.","Su, J.","Leman, S.","Guisquet, A. M. Le","Ibarguen-Vargas, Y.","Joeyen-Waldorf, J.","Glorioso, C.","Tseng, G. C.","Pezzone, M.","Hen, R.","Belzung, C."],"author_short":["Sibille, E.","Su, J.","Leman, S.","Guisquet, A.<nbsp>M.<nbsp>L.","Ibarguen-Vargas, Y.","Joeyen-Waldorf, J.","Glorioso, C.","Tseng, G.<nbsp>C.","Pezzone, M.","Hen, R.","Belzung, C."],"bibtex":"@article{ sibille_lack_2007,\n title = {Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity},\n volume = {12},\n issn = {1359-4184},\n doi = {10.1038/sj.mp.4001990},\n abstract = {Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-{HT}) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-{HT} system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-{HT}(1B) receptor (5-{HT}(1B)R), a candidate gene for 5-{HT}-mediated age-related functions. We show that the lack of 5-{HT}(1B)R (Htr1b({KO}) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b({KO}) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b({KO}) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b({KO}) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems ({IGF}-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-{HT} function, thus identifying 5-{HT} as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-{HT}.},\n language = {eng},\n number = {11},\n journal = {Molecular Psychiatry},\n author = {Sibille, E. and Su, J. and Leman, S. and Le Guisquet, A. M. and Ibarguen-Vargas, Y. and Joeyen-Waldorf, J. and Glorioso, C. and Tseng, G. C. and Pezzone, M. and Hen, R. and Belzung, C.},\n month = {November},\n year = {2007},\n pmid = {17420766},\n pmcid = {PMC2515886},\n keywords = {Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Dopamine Plasma Membrane Transport Proteins, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Hand Strength, In Situ Hybridization, Maze Learning, Mice, Mice, Knockout, Microarray Analysis, Motor Activity, Reaction Time, Receptor, Serotonin, 5-{HT}1B, Survival Analysis},\n pages = {1042--1056, 975}\n}","bibtype":"article","doi":"10.1038/sj.mp.4001990","id":"sibille_lack_2007","issn":"1359-4184","journal":"Molecular Psychiatry","key":"sibille_lack_2007","keywords":"Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Dopamine Plasma Membrane Transport Proteins, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Hand Strength, In Situ Hybridization, Maze Learning, Mice, Mice, Knockout, Microarray Analysis, Motor Activity, Reaction Time, Receptor, Serotonin, 5-HT1B, Survival Analysis","language":"eng","month":"November","number":"11","pages":"1042--1056, 975","pmcid":"PMC2515886","pmid":"17420766","title":"Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity","type":"article","volume":"12","year":"2007","bibbaseid":"sibille-su-leman-guisquet-ibarguenvargas-joeyenwaldorf-glorioso-tseng-pezzone-hen-belzung-lackofserotonin1breceptorexpressionleadstoagerelatedmotordysfunctionearlyonsetofbrainmolecularagingandreducedlongevity-2007","role":"author","urls":{},"keyword":["Age Factors","Aging","Analysis of Variance","Animals","Animals","Newborn","Behavior","Animal","Dopamine Plasma Membrane Transport Proteins","Enzyme-Linked Immunosorbent Assay","Gene Expression","Gene Expression Regulation","Hand Strength","In Situ Hybridization","Maze Learning","Mice","Mice","Knockout","Microarray Analysis","Motor Activity","Reaction Time","Receptor","Serotonin","5-HT1B","Survival Analysis"],"downloads":0,"html":""},"bibtype":"article","biburl":"http://bibbase.org/zotero/brizard","creationDate":"2015-02-11T09:04:27.329Z","downloads":0,"keywords":["age factors","aging","analysis of variance","animals","animals","newborn","behavior","animal","dopamine plasma membrane transport proteins","enzyme-linked immunosorbent assay","gene expression","gene expression regulation","hand strength","in situ hybridization","maze learning","mice","mice","knockout","microarray analysis","motor activity","reaction time","receptor","serotonin","5-ht1b","survival analysis"],"search_terms":["lack","serotonin1b","receptor","expression","leads","age","related","motor","dysfunction","early","onset","brain","molecular","aging","reduced","longevity","sibille","su","leman","guisquet","ibarguen-vargas","joeyen-waldorf","glorioso","tseng","pezzone","hen","belzung"],"title":"Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity","year":2007,"dataSources":["H9yznXMN7R8ae2jTA"]}